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The effects of IGF-1 and erythropoietin on apoptosis and telomerase activity in necrotizing enterocolitis model

Abstract

Background

Apoptosis that occurs after hypoxia/reoxygenation (H/R) has an important role in the pathogenesis of necrotizing enterocolitis (NEC). Telomerase activity, showing the regeneration capacity, may also be important in the recovery process. Therefore, we aimed to investigate the effects of insulin-like growth factor-1 (IGF-1) and erythropoietin (EPO) on apoptosis and telomerase activity in an H/R model.

Methods

Young mice were divided into four groups each containing ten Balb/c mice. Group 1 (H/R) were exposed to H/R; group 2 and group 3 were pretreated with IGF-1 and EPO, respectively, for 7 days before H/R. Group 4 served as control. Intestinal injury was evaluated by histological scoring and assessment of apoptosis was performed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) test. Proapoptotic and antiapoptotic gene expressions and telomerase activity were analyzed by real-time PCR.

Results

IGF-1- and EPO-treated animals had decreased histological damage and apoptosis, confirmed by TUNEL test and caspase activity. Telomerase activity was increased in these animals in addition to increased expression of antiapoptotic genes. However, proapoptotic gene expressions were not statistically different.

Conclusions

The protective effects of IGF-1 and EPO in H/R damage may be through increased expression of antiapoptotic genes and increased telomerase activity, especially for IGF-1.

Impact

  • This is a comprehensive study measuring various variables, namely IGF-1, EPO, apoptosis, apoptotic and antiapoptotic genes, and telomerase activity in the NEC model.

  • The intestinal protective effects of IGF-1 and EPO in H/R damage may occur through increased expression of antiapoptotic genes and increased telomerase activity.

  • To the best of our knowledge, telomerase activity has not been investigated in the NEC model before.

  • Regarding our results, novel strategies may be implemented for the early definitive diagnosis, robust preventive measures, and effective treatment modalities for NEC.

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Fig. 1: Hematoxylin and eosin staining of the intestinal tissue of study groups (microscopic view, ×40).
Fig. 2: The number of apoptotic cells found in study groups.
Fig. 3: Fluorescence microscopic view of TUNEL assay results (microscopic view, ×40).
Fig. 4: Caspase-3 levels detected in study groups.
Fig. 5: Relative antiapoptotic gene levels among study groups detected by real-time RT-PCR.
Fig. 6: Relative TERT expression levels among study groups.

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Acknowledgements

This study was granted by “The Scientific and Technological Research Council of Turkey” (TUBITAK).

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Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: M.A., B.D., O.A.K., S.U., and U.A. Drafting the article or revising it critically for important intellectual content: M.Y., H.A., and O.C. Final approval of the version to be published: M.A., B.D., M.B., F.O., and N.K.

Corresponding author

Correspondence to Burak Durmaz.

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Akisu, M., Durmaz, B., Koroglu, O.A. et al. The effects of IGF-1 and erythropoietin on apoptosis and telomerase activity in necrotizing enterocolitis model. Pediatr Res 90, 559–564 (2021). https://doi.org/10.1038/s41390-020-01195-7

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